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Biomedicine

A Better Artificial Skin

Skin cells genetically engineered to be resistant to bacteria could reduce infections and improve chances of survival among burn victims.

A patient’s skin cells, genetically modified and grown in a test tube, could provide the next generation of artificial skin. As a first step in creating such replacement skin, scientists in Cincinnati have engineered bacteria-resistant skin cells in the lab and are now testing them in animals. Ultimately, they hope to produce a type of artificial skin that can sweat, tan, and fight off infection.

Genetically modified skin cells may help protect cultured skin substitutes from infection. Here, cells that were genetically modified to produce higher levels of a protein known as human beta defensin 4 are shown in green.

“We’re using genetic modification to try to get the cultured skin to behave more like normal skin,” says Dorothy Supp, a researcher at the Cincinnati Shriners Hospital for Children who led the project.

Skin keeps us hydrated, cools us with sweat, and forms a blockade against foreign bacteria. Without skin’s protective covering, victims of severe burns suffer serious dehydration and are vulnerable to life-threatening bacterial infections. Grafts of healthy skin on the injured areas can help, but people with large burns often don’t have enough healthy skin to graft.

Over the past decade, artificial-skin products–made from scaffolds of collagen, the molecule that gives skin its structure and elasticity–have drastically improved burn victims’ chances of survival. Large sheets of the flexible mesh placed over open wounds encourage growth of new dermis, the bottom layer of skin, which does not regenerate under normal circumstances. Surgeons can then transplant small pieces of the patient’s epidermis, the top layer of skin, which grows and spreads over the newly grown dermis.

More recently, scientists have begun seeding the collagen scaffolds with skin cells to help the skin grow: rather than transplanting epidermis onto newly grown skin, scientists grow epidermis cells on the collagen scaffold and then transplant the entire sheet. In an experimental method developed by Steven Boyce of the University of Cincinnati, a patient’s own skin cells are biopsied and then grown in culture. The cells attach to a collagen scaffold, forming a skinlike structure and generating sheets up to 100 times the size of the original biopsy.

One of the remaining major problems with artificial skin is its vulnerability infection. It can take a week or two for blood vessels, which carry the immune system’s infection-fighting machinery, to connect to the newly growing dermis. “Without blood vessels, bacteria can grow and cause infection, and may destroy the graft and open the wound once more,” says Ioannis Yannas, a bioengineer and materials scientist at MIT who helped develop the first artificial-skin product. Currently, doctors must continually wrap wounds with antibacterial bandages.

So Supp and colleagues genetically modified skin cells to produce higher levels of an antibacterial protein. In a paper published in the current issue of the Journal of Burn Care and Research, Supp showed that these skin cells, when grown in a test tube, could kill more of a specific kind of bacteria than standard skin cells.

Supp cautions that the engineered cells are still a long way from clinical use. The true test of the bacteria-fighting properties will come in the complex environment of a real wound, which is littered with many different types of bacteria. The researchers are now planning experiments in animal models.

Ideally, Supp wants to create even better cultured skin, with cells that can grow the molecular structures required to produce sweat, hair, and pigment. “If we can start with two cell types and add one or two genes at a time and get these structures to develop, that would be very exciting,” she says.

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